A-Alkylidene y-butyrolactones

The reaction shown in Eq. 9.47 demonstrates a short synthesis ofy-[(trityloxy)methyl]-a-alkylidene-y-butyrolactones having stereodefmed mono- and disubstituted exo-alkylidene... 

The a-alkylidene-y-butyrolactone 3 is isomerized by this method to the buten-olide 4. 

Divalent palladium-catalyzed clization of allylic alkynoates yields a-alkyliden-y-butyrolactones <94PAC1501,93JCR(S)366>. 

Allylic alkynoates are a group of special enynes with an electron-deficient triple bond and an ester linkage between the double bond and triple bond. Based on the reaction described in Sect. B.iv.a, an intramolecular version could be developed, for example, au a-alkylidene-y-butyrolactone structure could easily be assembled through halopallada-tion, carbon-carbon double bond insertion, and dehalopalladation " (Scheme 13). The mechanism may be sununatized as shown in Scheme... 

Straightforward stereocontrolled methods for synthesizing both geometric isomers of a-alkylidene-y-butyrolactones have been reported. Following successive treatment with LDA and the readily available bis[methoxy(thiocarbonyl)] disulphide, y-butyrolactone reacts with aldehydes to give predominantly E-a-alkylidene-y-butyrolactones. The presence of a metal salt [e.g. copper(l) iodide or zinc chloride] dramatically alters the stereochemical outcome of the reaction (e.g. Scheme 56). 

Alizadeh, A., Sabahnoo, H., Noaparast, Z., Zohreh, N., and Mikaeili, A. (2010) One-pot synthesis of a-alkylidene-Y-butyrolacton-2-ones (tetronic acid derivatives) Polar solvent induces a new type of Y-lactonization. Synlett., 1854-1858. 

The prochiral MBH substrates (360) have been converted into a-alkylidene-y-butyrolactones (361) with <98% ee via the intramolecular Rauhut-Currier reaction, catalysed by the L-valine-derived tosylamido phosphine (362). ... 

Following these examples, methylene cyclopropene and certain 5,6-dihydrocali-cenes are now obtainable. Adding lithio trimethylsilylcyclopropanes to aldehydes also provides alkylidene cyclopropanes (Peterson olehnation route) . An approach to a-methylene y-butyrolactones starting with dibromocyclopropanes has been opened by a suitable manipulation of intermediate cyclopropyl anions (equation 133). ... 

Acid-promoted lactonization of y-hydroxy esters is an important way to construct lactones. For example, Scolastico and co-workers first reported the lactonization of MBH adducts 213 using 0.7 m HCl in ACOH-H2O, obtaining cx-methylene-p-hydroxy-5-butyrolactones 215a,b in moderate yields (Scheme 4.65). Trifluoroacetic acid, CSA and sulfuric acid were also used in such lactonizations. In an alternative method, ot-methylene-p-hydroxy-8-butyrolactone 215c was synthesized by the intramolecular MBH reaction in 62% yield (Scheme 4.66). A series of a-alkylidene-8-butyrolactones and multi-substituted a-methylene-8-butyrolactones have been synthesized from MBH adducts (Figure 4.2). 

The diastereoselectivity in the Pd(II)-LiX-CuX2-catalyzed cyclization of 2 -alkenyl 2-alkynoates is similar to that in the Pd(II)-LiX-catalyzed cyclization of 4 -het-eroatom-2 -alkenyl 2-alkynoates. The similar diastereoselectivity was observed in the synthesis of a-alkylidene-y-butyrolactams. The diastereoselectivity is further supported by the cascade cyclization reaction. A monocyclic product was obtained in the reaction of l, 5 -hexadien-3 -yl propynoate. The failure of the second cyclization might be due to the trans-configuration of the /S.y-disubstituents in the product. The reaction of r,5 -hexadien-3 -yl 3-substituted 2-aIkynoates under the same conditions yielded the cw-fused bicyclic a-(Z)-chloroalkylidene- y-butyrolactone derivatives implying the cw-diastereochemistry of the /3,y-disubstituents in the first cyclization (Scheme 16). 

As discussed in Sect. V.3.5, halide ions can also add to the palladium 7r-complexes, and the process may be termed halopalladation. Addition of Pd and a halogen, such as Cl and Br, to olefins, acetylenes, allenes, and conjugated dienes has been reported. However, most of the currently useful reactions initiated by halopalladation involve the use of alkynes as the substrates. Halopalladation of aUcynes gives vinylpalladium intermediates, which can undergo intramolecular carbopalladation to form cyclized products. Pd-catalyzed cyclization of ally lie aUcynoates can produce 7r-alkylidene-y-butyrolactones, which represent a basic structural unit in a wide variety of biologically active natural products. 

The convenient synthetic methodology for the a-silyl esters has been ejrtended to the synthesis of a-alkylidenelactones [198, 199]. Peterson reactions of the carban-ion generated from a-silyl-y-butyrolactones 117 with carbonyl compounds afford the corresponding a-alkylidene-y-lactones 118 with high -selectivity (Scheme 2.71). The yields are low when ketones are used as substrates. 

P,P-Disubstituted alkylidene derivatives of oxindole, azlactone, and y-butyrolactone are used as precursors of vinylogous enolates, which are highly stabilized owing to the heteroaromatic nature of the enolate components. Although these a,p-unsaturated carbonyl systems can act as electrophilic Michael acceptors, the presence of two p-substituents seems to suppress nucleophilic attack on the P-carbon. 

Synthesis of a series of novel functionalized achiral and chiral allyl boronates has been recently reported by Ramachandran via nucleophilic SNj -type addition of copper boronate species (generated from the boronates 37, 141, 142 under Miyaura conditions) [115,116] to various functionalized allyl acetates that tvere prepared either via vinylalumination or by Baylis-Hillman reaction with various aldehydes [117]. The resulting allylic boronates bearing an ester moiety (X=OR) were subsequently used for the synthesis of a-alkylidene-/3-substituted-y-butyrolactones by allylboration of aldehydes (Scheme 3.76). 

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